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长链非编码 RNA 的 microRNA 结合位点多态性与中国汉族人群结直肠癌的风险和预后相关。

MicroRNA Binding Site Polymorphisms of the Long-Chain Noncoding RNA are Associated with Risk and Prognosis of Colorectal Cancer in Chinese Han Population.

机构信息

Department of Colorectal Surgery, The Third People's Hospital of Hangzhou, Hangzhou, China.

School of Life Science, HuZhou University, Huzhou Cent Hosp, Huzhou, China.

出版信息

Genet Test Mol Biomarkers. 2020 May;24(5):239-248. doi: 10.1089/gtmb.2020.0013. Epub 2020 Apr 28.

Abstract

The metastasis-associated lung adenocarcinoma transcript 1 () gene's rs664589 locus is located within the binding site of the miRNA hsa-miR-194-5p for its cognate long-chain noncoding RNA (lncRNA) MALAT1. The aim of this study was to investigate the association between the rs664589 single nucleotide polymorphism (SNP) and the risk and prognosis of colorectal cancer (CRC) in the Chinese Han population. A cohort of 340 patients with CRC who underwent surgical resection and another group of 340 healthy subjects were enrolled in this study and analyzed for their rs664589 genotypes. In addition, quantitative real-time-polymerase chain reaction was used to detect the expression levels of the lncRNA MALAT1 and the hsa-miR-194-5p in cancer tissues and paracancerous normal tissues of CRC patients. The risk of CRC in subjects carrying the G allele at the rs664589 locus in the 3' untranslated region of the gene was 1.81 times higher than for C allele carriers. The expression levels of the in cancer tissues was significantly higher than that in paracancerous tissues, while the hsa-miR-194-5p expression level was significantly lower in cancerous tissues compared to cognate paracancerous tissues. The progression-free survival (PFS) rate for patients with the gene rs664589 locus GG genotype was significantly lower than that of CG genotype patients. Moreover, inhibited the expression of hsa-miR-194-5p. The risk of CRC was relatively higher among rs664589 G allele carriers, and the CRC patients with a G allele had a lower PFS. The likely mechanism underlying these observations is that the rs664589 SNP affects the binding efficiency between the and the miRNA has-miR-194-5p, although this awaits laboratory confirmation.

摘要

转移相关肺腺癌转录物 1 () 基因的 rs664589 位点位于其同源长链非编码 RNA (lncRNA) MALAT1 的 miRNA hsa-miR-194-5p 结合位点内。本研究旨在探讨中国汉族人群中 rs664589 单核苷酸多态性 (SNP) 与结直肠癌 (CRC) 风险和预后的关系。

本研究纳入了 340 例接受手术切除的 CRC 患者队列和另外 340 例健康对照者,分析了他们的 rs664589 基因型。此外,采用实时定量聚合酶链反应检测 CRC 患者癌组织和癌旁正常组织中 lncRNA MALAT1 和 hsa-miR-194-5p 的表达水平。

携带基因 3'非翻译区 rs664589 位点 G 等位基因的受试者发生 CRC 的风险是携带 C 等位基因的 1.81 倍。癌组织中基因的表达水平明显高于癌旁组织,而癌组织中 hsa-miR-194-5p 的表达水平明显低于相应的癌旁组织。携带基因 rs664589 位点 GG 基因型的患者无进展生存期 (PFS) 率明显低于 CG 基因型患者。此外,抑制了 hsa-miR-194-5p 的表达。携带基因 rs664589 位点 G 等位基因的 CRC 风险相对较高,且携带 G 等位基因的 CRC 患者 PFS 较低。这些观察结果的可能机制是 rs664589 SNP 影响了基因与 miRNA 之间的结合效率。

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